The primary objective of this project is to develop new synthetic methodology based on reactions of organometallic complexes with organic substrates. The work particularly emphasizes development of new reactions using simple model systems coupled with thorough mechanistic studies. This approach provides new methodology for use in synthesis as well as a broad, general understanding of the ways in which transition metal complexes may be used to control organic reactions including regio- , stereo- and enantioselectivity. One specific aim of the work is to use nucleophilic, electron-rich organomanganese and organoiron complexes to effect coupling with carbon electrophiles via addition of the electrophile to the metal center followed by migration to the pi-bound organic ligand. Using this general approach, methods will be developed for (a) regio- and stereocontrolled electrophilic substitutions of dienes, (b) stepwise, regioselective electrophilic substitutions of arenes and (c) coupling of substituted pi-allyl groups to carbon electrophiles with regioselectivity controlled via choice of metal ligands. A second aspect of the project will focus on reactions of electrophilic chiral-at-iron carbene complexes. Routes to several optically pure iron carbene complexes will be devised. These complexes will then be used to develop new enantioselective syntheses of alcohol and ethers, epoxides, aziridines and alpha-lithioethers. Mechanistic studies will be aimed at revealing the basis for enantioselection and how variations in ligand environment control enantioselectivity. New reactions developed will complement existing synthetic methodology and should be applicable to the preparation of a diverse class of naturally occurring and/or biologically active systems. For example, the regio- and stereospecific electrophilic substitution of dienes could provide methods for the synthesis of intermediates which are readily converted by Diels-Alder reactions to aspidosperma alkaloids and cytochalasans, compounds which affect a range of biological processes including cell movement, platelet aggregation, cytokinesis and phagocytosis. The chiral iron systems can provide several enantiomerically pure chiral "building blocks" which can be used in synthesis. The enantioselective cyclopropanation reaction will supply methodology for preparation of a variety of naturally occurring compounds containing cyclopropane rings. Such reagents are particularly attractive for use in synthesizing calysterols, naturally occurring steroids containing monomethyl-substituted cyclopropane and cyclopropene rings.